抗P-糖蛋白多肽模拟物的设计、合成与活性评价抗P-糖蛋白多肽模拟物的设计、合成与活性评价

Structure-based design， synthesis and evaluation of bioactivity of anti-P-gp peptide mimetic

摘要: 目的设计、合成抗P-糖蛋白抗体（PHMA02）的多肽模拟物，测定其与P-gp结合活性。方法模建出PHMA02的互补决定簇（complementarity-determining region, CDR）三维结构，构建出抗P-gp的多肽模拟物。流式细胞仪测定其活性。结果该模拟物竞争P-gp抗体与P-gp结合，并部分阻断P-gp药物外排泵的功能。结果显示抗P-gp肽模拟物对P-gp具有相同结合活性。结论根据抗体CDR区的构象特征可以构建具有生物活性的肽模拟物。基于抗体结构的药物设计将推动药物研究的发展。

Abstract: AimTo design and evaluate the small peptide mimetic of anti-P-glycoprotein ( P-gp ) antibody (PHMA02 ). MethodsFrom the three dementional structure analysis of computer modeling of PHMA02 CDR loops, a small peptide mimetic was designed and determined by flow cytometry. ResultsAnti-P-gp peptide mimetic functionally similar to PHMA02 was developed. The peptide mimetic competitively inhibits PHMA02 binding to P-gp and partially block the P-gp function as a drug efflux pump in K562/A02 cells. ConclusionSome special conformational properties of CDR loops of antibody might serve as lead structures for develop new biological peptide mimetics. Antibody-structure-based design would develop new drug in the future.